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. 2015 Aug 20;10(8):e0134550.
doi: 10.1371/journal.pone.0134550. eCollection 2015.

Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study

Eric Kaplovitch  1 , Tara Gomes  2 , Ximena Camacho  3 , Irfan A Dhalla  4 , Muhammad M Mamdani  2 , David N Juurlink  4
Affiliations

Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study

Eric Kaplovitch et al. PLoS One. .

Abstract

Background: The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown.

Methods and findings: We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53). These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy.

Conclusions: Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated.

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Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts: Dr. Muhammad Mamdani has received honoraria from Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Bayer. Dr. Mamdani has served as an Advisory Board member for the following pharmaceutical companies: Astra-Zeneca, Bristol-Meyers Squibb, Eli Lilly and Company, Glaxo Smith Kline, Hoffman La Roche, Novartis, Novo Nordisk, Pfizer. Irfan A. Dhalla serves in a voluntary capacity on the National Advisory Committee on Prescription Drug Misuse, which is organized by the Canadian Centre for Substance Abuse, a non-governmental organization funded by the Canadian federal government. Irfan A. Dhalla also serves in a voluntary capacity on the Board of Directors of Physicians for Responsible Opioid Prescribing.

Figures

Fig 1
Fig 1. Escalation to high dose opioid therapy among men and women.
Kaplan-Meier curves of opioid dose escalation to an average daily dose exceeding 200 mg of morphine (or equivalent) among men and women with at least 91 days of continuous opioid therapy. P values were determined by Cox proportional hazards regression.
Fig 2
Fig 2. Opioid-related death among men and women.
Kaplan-Meier curves of opioid-related mortality among men and women with at least 91 days of continuous opioid therapy. P values were determined by Cox proportional hazards regression.
See this image and copyright information in PMC

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